Safety of an adenovirus serotype 5-vectored HIV-1 Gag/Pol/Env vaccine

Stephen Voght

For several years, the recombinant adenovirus serotype-5 (Ad5) vaccine vector was the prime candidate for creating an effective HIV-1 vaccine, due to its safety, tolerability and robust induction of an immune response in most individuals. Several HVTN clinical trials were initiated studying variations of vaccines based on this vector, including the Step study, a large Phase II trial that was halted in 2007 due to the candidate vaccine’s inability to prevent HIV infection. HVTN protocol 054 evaluated the safety and immunogenicity of a candidate Ad5-vectored HIV-1 vaccine developed by the National Institutes of Health Vaccine Research Center. The vaccine included inserts for the HIV-1 Gag, Pol and Env proteins. To minimize potential causes of immunological variation, participants were required to not have pre-existing Ad5 antibodies. Participants received a single vaccination at one of two dose levels, local and systemic responses were monitored, and the resulting immune responses were evaluated to determine the immunogenicity of the vaccine. The trial was evaluated by VIDD staff scientists Cecilia Morgan and Zoe Moodie, VIDD affiliate investigator Stephen De Rosa, VIDD co-director Julie McElrath and colleagues.

Side-effects were minimal at either dose, and the vaccine was generally well tolerated by recipients. When assayed one month after vaccination, more than 85% of vaccinees had detectable HIV-1 specific T-cell responses, which persisted until at least one year following vaccination. Increasing the dose had a minimal effect on the strength of the response. The vaccine also induced antibodies against HIV-1 Envelope in all vaccine recipients, although the titers were relatively low. However, following the unexpected negative results from the Step study, the future of Ad5-vectored HIV-1 vaccines is now unclear.